Vandetanib at 300 mg in combination with Bicalutamide at 50 mg will be administered orally, daily and continuously

Drug: Vandetanib

Vandetanib at 300 mg in combination with Bicalutamide at 50 mg will be administered orally, daily and continuously

Active Comparator: B

Bicalutamide at 50 mg will be administered orally, daily and continuously.

Drug: Bicalutamide

Bicalutamide at 50 mg will be administered orally, daily and continuously.

Detailed Description:

With the advent of PSA surveillance, many patients diagnosed with hormone refractory disease, have PSA rising disease only, are asymptomatic, with no evidence of metastatic disease. There is no standard of care in this patient population. A standard treatment in this population has been the addition of a non-steroidal anti androgen such as bicalutamide. PSA response rate (defined as a 50% decrease) have been reported in 20% range with bicalutamide.

Even in patients with hormone refractory prostate cancer (HRPC) and metastases that have no cancer related symptoms, initiation of chemotherapy is controversial given the palliative nature of chemotherapy and potential for serious toxicity.

These patients are generally well enough to to undergo trials of novel agents and achieve adequate drug exposure, such that any cytostatic effect will be apparent.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have a pathological diagnosis of adenocarcinoma of the prostate

Patients must have biochemically recurrent disease or metastatic disease that is asymptomatic or minimally symptomatic (total daily morphine dose < 30mg.day) for which no curative therapy exists.

Patients must have documented evidence od PSA progression while receiving androgen ablative therapy (i.e. must be hormone refractory). Progression is defined as the development of new metastatic lesions, or rising PSA defined as at least two rises in PSA at least 1 week apart. If the second PSA is not rising, a thrid PSA is required to show further increase; if not, a subsequent level must show further increase. The third (or subsequent) PSA confirming progression must be within 2 weeks of randomization.

The PSA must be => 2ug/L at the time of study entry.

ECOG performance status of 0 or 1

Age =>18 years

Patients must have a life expectancy of at least 12 weeks

No Prior chemotherapy is permissible for hormone refractory disease. Chemotherapy may have been received in a neoadjuvant or adjuvant setting provided it was given 12 months prior to registration.

Hormone Therapy

Prior hormone therapy in the form of either medical or surgical castration is required. If the patient is receiving medical androgen abalation a castrate level of testosterone (1.7nmol/L) must be present. Therapy with LHRH agonist must continue for those prostate cancer patients already receiving this treatment at the time of registration. If the patients has discontinued the LHRH agonist, this must be restarted and a castrate level of testosterone must be present.

Prior use of nonsteroidal antiandrogens (including bicalutamide) is permitted but must have been discontinued 6 weeks prior to registration.

Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed between the last dose and registration in the trial. Exceptions will be made for limited field, single fraction palliative radiation to bone.

No concurrent treatment with steriods unless steriods have been ingested for 4 weeks prior to commencing study at a dose of less than or equal to an equivalent of prednisone 20mg per day.

No concurrent experimental trial medication is permitted. No prior use of VEGF/VEGFR or EGFR targeting agents for hormone refractory disease is permitted.

Baseline QTc (Bazett's) <480msec determined by the average of a least 3 consecutive electrocardiograms (ECG) taken within 5-10 mins of each other.

Patient consent must be obtained according to local institutional and/or University Research and Ethic Board (REB) requirements.

Patients must be accessible for treatment and follow up.

Protocol treatment is to begin within 7 calendar days of patient registration.

Exclusion Criteria:

Patients with a history of other invasive malignancy, except:adequately treated non melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for 3 years.

Patients with known brain metastases or leptomemingeal disease are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of nerologic and other adverse events.

History of allergic reactions and/or sensitivity attributed to compounds of similar chemical or biological composition to Vandetanib or other agents used in the study.

Upper gasrtointerstinal or other conditions that would preclude compliance with oral medication

Patients with immune deficiency are at increased risk of lethal infections when treated with Marrow-suppressive therapy. Therefore, HIV positive patients receiving combination ant-retroviral therapy are excluded from study because of possible risk of lethal infection and additionally because of the possible pharmacokinetic interactions with Vandetanib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

Patients who require escalating amounts of narcotic therapy to control pain e.g. morphine equivalent dose >30mg/day) since these patients would more appropriately be offered systemic chemotherapy

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00757692